PMID- 35608792
OWN - NLM
STAT- MEDLINE
DCOM- 20220608
LR  - 20220628
IS  - 1976-3786 (Electronic)
IS  - 0253-6269 (Linking)
VI  - 45
IP  - 5
DP  - 2022 May
TI  - Adapalene induces adipose browning through the RARbeta-p38 MAPK-ATF2 pathway.
PG  - 340-351
LID - 10.1007/s12272-022-01384-4 [doi]
AB  - Adipose browning has recently been reported to be a novel therapeutic strategy 
      for obesity. Because the retinoic acid receptor (RAR) is a potential target 
      involved in browning, adapalene (AD), an anti-acne agent with RAR agonism, was 
      examined in detail for its effects on adipose browning and the underlying 
      mechanisms in vitro and in vivo. AD upregulated the expression of adipose 
      browning-related markers in a concentration-dependent manner, promoted 
      mitochondrial biogenesis, increased oxygen consumption rates, and lowered lipid 
      droplet sizes in differentiated 3T3/L1 white adipocytes. Among the three retinoic 
      acid receptors (RARalpha, RARbeta, and RARgamma), knockdown of the gene encoding RARbeta 
      mitigated AD-induced adipose browning. Similarly, LE135 (a selective RARbeta 
      antagonist) attenuated AD action, suggesting that AD promotes adipose browning 
      through RARbeta. Sequential phosphorylation of p38 mitogen-activated protein kinase 
      (MAPK) and activating transcription factor 2 (ATF2) was critical for AD-induced 
      adipose browning, based on the observations that either SB203580 (a p38 MAPK 
      inhibitor) or ATF2 siRNA reduced the effects of AD. In vivo browning effects of 
      AD were confirmed in C57BL/6J mice and high-fat diet-induced obese (DIO) mice 
      after oral administration of AD either acutely or chronically. This study 
      identifies new actions of AD as an adipose browning agent and demonstrates that 
      RARbeta activation followed by increased phosphorylation of p38 MAPK and ATF2 
      appears to be a key mechanism of AD action.
CI  - (c) 2022. The Pharmaceutical Society of Korea.
FAU - Lee, Na Hyun
AU  - Lee NH
AD  - Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 
      21999, Republic of Korea.
FAU - Choi, Mi Jin
AU  - Choi MJ
AD  - Department of Pharmacology, Gachon University School of Medicine, Incheon, 21999, 
      Republic of Korea.
FAU - Yu, Hana
AU  - Yu H
AD  - Department of Pharmacology, Gachon University School of Medicine, Incheon, 21999, 
      Republic of Korea.
FAU - Kim, Jea Il
AU  - Kim JI
AD  - Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 
      21999, Republic of Korea.
FAU - Cheon, Hyae Gyeong
AU  - Cheon HG
AD  - Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 
      21999, Republic of Korea. hgcheon@gachon.ac.kr.
AD  - Department of Pharmacology, Gachon University School of Medicine, Incheon, 21999, 
      Republic of Korea. hgcheon@gachon.ac.kr.
LA  - eng
GR  - 2020R1F1A1048327/Ministry of Education/
PT  - Journal Article
DEP - 20220524
PL  - Korea (South)
TA  - Arch Pharm Res
JT  - Archives of pharmacal research
JID - 8000036
RN  - 0 (Activating Transcription Factor 2)
RN  - 0 (Atf2 protein, mouse)
RN  - 0 (Lipid Regulating Agents)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (retinoic acid receptor beta)
RN  - 1L4806J2QF (Adapalene)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - 3T3-L1 Cells
MH  - *Activating Transcription Factor 2/metabolism
MH  - *Adapalene/administration & dosage/pharmacology
MH  - *Adipose Tissue, White/drug effects/metabolism
MH  - Administration, Oral
MH  - Animals
MH  - *Lipid Regulating Agents/administration & dosage/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phosphorylation
MH  - *Receptors, Retinoic Acid/metabolism
MH  - *p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - Adapalene
OT  - Adipose browning
OT  - Obesity
OT  - Retinoic acid receptor beta
EDAT- 2022/05/25 06:00
MHDA- 2022/06/09 06:00
CRDT- 2022/05/24 11:21
PHST- 2021/12/27 00:00 [received]
PHST- 2022/05/16 00:00 [accepted]
PHST- 2022/05/25 06:00 [pubmed]
PHST- 2022/06/09 06:00 [medline]
PHST- 2022/05/24 11:21 [entrez]
AID - 10.1007/s12272-022-01384-4 [pii]
AID - 10.1007/s12272-022-01384-4 [doi]
PST - ppublish
SO  - Arch Pharm Res. 2022 May;45(5):340-351. doi: 10.1007/s12272-022-01384-4. Epub 
      2022 May 24.